L-2-HGA affects the
central nervous system, with clinical signs usually apparent between
6 months and one year (although they can appear later). Symptoms
include epileptic seizures, “wobbly” gait, tremors, muscle stiffness
as a result of exercise or excitement and altered behaviour.

The mutation, or
change to the structure of the gene, probably occurred spontaneously
in a single dog but once in the population has been inherited from
generations to generation like any other gene. The disorder shows
an autosomal recessive mode of inheritance: two copies of the
defective gene (one inherited from each parent) have to be present
for a dog to be affected by the disease. Individuals with one copy
of the defective gene and one copy of the normal gene – called
carriers – show no symptoms but can pass the defective gene onto
their offspring. When two apparently healthy carriers are crossed,
25% (on average) of the offspring will be affected by the disease,
25% will be clear and the remaining 50% will themselves be carriers.

The mutation
responsible for the disease has recently been identified at the
Animal Health Trust. Using the information from this research, we
have developed a DNA test for the disease. This test not only
diagnoses dogs affected with this disease but can also detect those
dogs which are carriers, displaying no symptoms of the disease but
able to produce affected pups. Carriers could not be detected by
the tests previously available which involved either a blood or
urine test detecting elevated levels of L-2-hydroxyglutarate or
magnetic resonance imaging. Under most circumstances, there will be
a much greater number of carriers than affected animals in a
population. It is important to eliminate such carriers from a
breeding population since they represent a hidden reservoir of the
disease that can produce affected dogs at any time.

The test is
available now and information on submitting samples is given below.
Breeders will be sent results identifying their dog as belonging to
one of three categories:

CLEAR:

The dog has
2 copies of the normal gene and will neither develop
L-2-HGA, nor pass a copy of the L-2-HGA gene to any of its
offspring.

CARRIER:

The dog has
one copy of the normal gene and one copy of the mutant gene
that causes L-2-HGA. It will not develop L-2-HGA but will
pass on the L-2-HGA gene to 50% (on average) of its
offspring.

AFFECTED:

The dog has
two copies of the L-2-HGA mutation and is affected with
L-2-HGA. It will develop L-2-HGA at some stage during its
lifetime, assuming it lives to an appropriate age.

Carriers can still be bred to clear dogs. On average, 50% of such a
litter will be clear and 50% carriers; there can be no affected pups
produced from such a mating. Pups which will be used for breeding
can themselves be DNA tested to determine whether they are clear or
carriers.